pathology of the hematopoietic systempeople.upei.ca/hanna/hemato-l2/hemat-l2-2014web.pdf · •...

Pathology of the Hematopoietic

System

Lecture 2:

Myeloproliferative diseases

Lymph nodes

Paul Hanna,

Fall 2014

Hematopoietic Neoplasia

Lymphoproliferative Disease

Lymphoma

Lymphoid leukemia

Plasma cell tumours

Myeloproliferative

Disease

Histiocytic Neoplasia

Myeloid leukemia

Myelodysplastic Syndrome

Mast cell tumour?

Primary Hematopoietic Neoplasia

Histiocytic proliferative / neoplastic disorders

1. Cutaneous histiocytoma

• common benign skin mass

• young dogs

• spontaneously regress

2. Reactive histiocytosis

• immunoregulatory disease

• proliferation of dermal/interstitial dendritic cells

• waxing & waning / slowly progressive

vetmedicine.about.com

Cutaneous reactive histiocytosis

• multiple skin masses

Systemic reactive histiocytosis

• skin, lymph nodes & viscera


33. Histiocytic Sarcoma

• malignant neoplasia of histiocytes

(macrophages or dendritic cells)

• breed predispositions

Bernese Mountain dog,

Rottweiler, Flat-coated retriever

• solitary lesions

periarticular, skin / subcutis,

lymph nodes, spleen or liver

• multisystemic lesions

disseminated histiocytic sarcoma

= malignant histiocytosis

Dr E Aburto

• aggressive multisystemic disease

tumor masses in many organs, eg spleen,

liver, lung, BM, LN’s, CNS, (rarely skin)

Disseminated histiocytic sarcoma (= malignant histiocytosis)

Histiocytic sarcoma, hilar

& mesenteric lymph nodes

Courtesy of Dr A Lopez, AVC


Dr E Aburto

• histology: - diffuse infiltrates of atypical histiocytes

- may be avidly hemophagocytic non-regenerative anemia.

Disseminated histiocytic sarcoma (= malignant histiocytosis)

Hemophagocytic histiocytic sarcoma


Mast cell neoplasia

• common skin tumors of dogs

Cutaneous mast cell tumours

• rare, mostly cats.

• two main forms: splenic and intestinal

Systemic mastocytosis*

Mast cells are widely distributed in connective tissues - but originate in BM

For information only

• Gross: splenomegaly +/- nodular surface

• can metastasize to liver, BM, lung, etc

Systemic mastocytosis (visceral mast cell tumors)

Can also see diffuse

hepatic enlargement

Mast cell neoplasia

Note, with the splenic form of systemic mastocytosis,

see diffuse &/or nodular splenomegaly


Histology:

sheets of

neoplastic

mast cells

efface the

parenchyma

Mast cell neoplasia

Systemic mastocytosis (visceral mast cell tumors)

Toluidine Blue H&E


Secondary bone marrow neoplasia

• result of metastasis of a tumor from a distant site to the bone marrow

• can be a carcinoma or a sarcoma

Metastasis of a malignant pheochromocytoma to the rib, dog

Arrows show the interface between the

tumor (upper right) and the bone

marrow of the rib (lower left)

Image Courtesy of Dr A Lopez

Myelophthisis

= replacement of hematopoietic tissue within the bone marrow by abnormal tissue

fibrosis → myelofibrosis

neoplastic cells → leukemia, lymphoma, histiocytic sarcoma, etc

• may result in pancytopenia due to competition for space / nutrients

Dog: Replacement of bone marrow by lymphoma

Monocyte-macrophage system (MMS)

• blood monocytes & fixed macrophages

Discussion of diseases affecting the monocyte-macrophage

system are discussed in the various organ systems

Veterinary Immunology

Lymphoid Tissue: Lymph nodes

Normal lymph node, cow

Dr E Aburto

Lymph node

Function:

• filtration of lymph

• immune response

Structure:

• outer cortex ➝ follicles (mostly B cells)

• inner cortex ➝ paracortex (mostly T cells)

• medulla ➝ mostly B cells

Lymph circulation: Afferent lymphatics subcapsular sinuses trabecular sinuses medullary sinuses efferent lymphatics thoracic duct

Modified from Pathologic Basis of

Veterinary Disease

Lymph node

Noah’s Arkive

Normal lymph node, cow Function:

• filtration of lymph

• immune response

Structure:

• outer cortex ➝ follicles (mostly B cells)

• inner cortex ➝ paracortex (mostly T cells)

• medulla ➝ mostly B cells

Dr. James F. Thompson's Web Resources

Lymph node: Anthracosis

Lymph node: Miscellaneous changes

• black discoloration due to carbon within phagocytes

Lymph node: Hemorrhage

• can originate within the lymph node or in the tissues drained by the node

• red discolouration of the lymph nodes

Lymph node: General response to injury

Enlarged lymph nodes

Lymphoid hyperplasia

Lymphadenitis

Primary neoplasia

Secondary neoplasia

Small lymph nodes

atrophy / degeneration

hypoplasia

Two basic responses: decrease in size or increase in size

Lymph node atrophy / degeneration

Senile atrophy (aging)

Cachexia / malnutrition

Viral infection

• BVD

• FIV

• CDV

• FPV / CPV

Toxins / Drugs / Irradiation

Lesions:

• Gross: small lymph nodes

• Histo: lymphoid depletion /

degeneration

Small lymph nodes

Lymphadenopathy (lymphadenomegaly)

• enlargement of the lymph nodes, of unknown or unspecified cause

• can be localized or generalized


Markedly enlarged supramammary lymph

nodes (ie marked lymphadenopathy) from cow

with mastitis.

It is called lymphadenompathy (ie enlarge

lymph nodes of unknown cause) until

diagnostic testing (eg histopathology) is done

to determine the cause of the enlargement.

Benign reactive hyperplasia:

• immunological reaction = response to antigen or circulating interleukins

lymph nodes draining site of local infection or vaccination

also occurs during early stages of lymphadenitis

• can be localized or generalized

Lymph Node Hyperplasia

Gross:

• enlargement of node(s)

• may bulge on cut section

Cornell Veterinary Medicine

Normal

Benign reactive

hyperplasia

Peripheral lymph nodes from a cow with localized

dermatitis. The normal node above is from an area

where the overlying skin was normal. The enlarged

(hyperplastic) lymph node below was draining an area

with dermaitis due to Dermatophilus congolensis.


Histology:

• proliferation of lymphoid follicles with prominent germinal centers

• increased T cells in the paracortex

• +/- increased plasma cells in the medullary cords

Note, the number of lymphoid follicles has increased (hyperplasia), and all

have germinal centers (secondary follicles) indicating active proliferation of

B lymphocytes to form plasma cells in response to an antigenic stimulus.

Normal

Antigenic

stimulation

Lymph Node Hyperplasia

• an inflammatory response to an infectious agent within the node

(*vs reactive hyperplasia which is an antigen driven immunologic response*

Lymphadenitis

• esp regional lymph node draining a site

of inflammation & becoming infected

• with sepsis – multiple nodes involved

Cervical & mediastinal lymphadenitis with sepsis

Acute lymphadenitis


Gross lesions:

• enlarged, soft, wet, red lymph nodes

• often bulging & hyperemic on cut surface

• exudates are usually serous

Tracheobronchial

lymphadenitis

Figure 13-71 (Zachary) Acute lymphadenitis, tracheobronchial

lymph nodes, pig. The nodes are enlarged and reddened from

draining the pneumonic cranial lung lobes. Note the red

consolidation of the dorsal portion of the cranial lung lobes.

Acute lymphadenitis

Mesenteric lymphadenitis

Chronic lymphadenitis

Note tracheobronchial

lymphadenitis in a foal

with pneumonia due to

Rhodococcus equi

• with chronicity, inflamed lymph nodes become irregular and firm due to fibrosis

• chronic suppurative lymphadenitis vs chronic granulomatous lymphadenitis

Chronic Suppurative Lymphadenitis

• swollen lymph node with pus-filled area surrounded by fibrous capsule

= lymph node abscess

• response to pyogenic bacteria

• can fistulate to the skin surface

Chronic Suppurative Lymphadenitis http://www.que.at/images/pferde/Durse/strangles.jpg

• Streptococcus equi subsp equi

• inflammation of the URT →

abscesses in the mandibular,

retropharyngeal & parotid LN’s

• may fistulate to the surface

• can spread to the viscera →

“Bastard Strangles”

Equine Strangles

Fig. 13-74 (Zachary) Acute

suppurative lymphadenitis,

equine strangles

(Streptococcus equi ssp. equi),

dorsal view of larynx, left and

right retropharyngeal lymph

nodes, horse. The lymph nodes

are grossly distended with pus.

Pathogenesis:

• usually enters via contamination of shear wounds; rarely by inhalation

• drains to regional lymph nodes

• superficial nodes > internal nodes

prescapular LN

prefemoral LN

Caseous lymphadenitis: Corynebacterium pseudotuberculosis

• chronic suppurative lymphadenitis in sheep & goats

• ulcerative lymphangitis in horses and cattle

• pectoral abscesses in horses


• chronic suppurative inflammation and caseous necrosis

• as lesion progresses characteristic concentric laminations


Fig. 13-71 (Zachary) Caseous lymphadenitis, Corynebacterium

pseudotuberculosis, lymph node, sheep. The whole lymph node

has been replaced by an abscess containing mostly semifluid

yellowish pus. This is an early stage of caseous lymphadenitis,

before the pus has become inspissated and caseous.


Note, the concentric laminations often seen in

the abscesses of “caseous lymphadentitis” are

considered characteristic of the disease.

• some cases have systemic involvement with abscesses in the internal organs


Goat, caudal mediastinal lymph nodes: lymph

node abcesses


Dr E Aburto

Nodular granulomatous

lymphadenitis

Mycobacterium bovis

Mycobacterium avium subsp.

paratuberculosis

Actinobacillus lignieresii

Migrating parasitic larva

Diffuse granulomatous

lymphadenitis

Porcine Circovirus type 2

Histoplasma capsulatum

Blastomyces dermatitidis

Cryptococcus neoformans

• focal or multifocal, white-yellow nodules

• +/- caseous necrosis / mineralization

• enlarged, pale, dry, firm lymph nodes

• diffuse loss of architecture

Chronic Granulomatous Lymphadenitis

Gross: - enlargement of the lymph node with single to multiple pale caseous nodules,

often with gritty (mineralized) centers

- confluence of multiple lesions may produce locally extensive to generalized

(diffuse) involvement of the node

Bovine tuberculosis: Mycobacterium bovis

Fig. 1-19 (Zachary) Tuberculosis (Mycobacterium bovis),

lymph node, ox. The normal architecture of the lymph node has

been completely obliterated by multiple caseating granulomas,

typical of Mycobacterium bovis lesions. Note the caseous

necrosis characterized by a pale yellow, crumbly exudate

Note, in some cases of tuberculosis (such as the one above)

there is coalescing of multiple lesions which results in

generalized (diffuse) distribution of the inflammation

Nodular Granulomatous Lymphadenitis

Dr E Aburto

Histology: granulomas with central necrosis and mineralization surrounded by

epithelioid macrophages and multinucleated giant cells




Acid fast staining shows numerous acid-fast positive

bacilli within the macrophages and giant cells.

(note, mycobacteria are readily seen on acid-fast

stains, but not on routine H&E staining).

Histolopathology of lymph node, showing part of a large granuloma with caseous necrosis (right) surrounded by a zone of inflammatory cells

(left), ie epithelioid (large epithelial looking), macrophages, inflammatory giant cells (ie from fused macrophages), lymphocytes & plasma cells.

Histology: granulomas with central necrosis and mineralization surrounded by

epithelioid macrophages and multinucleated giant cells


Diffuse Granulomatous Lymphadenitis

Postweaning multisystemic wasting syndrome (PMWS):


Pig on the left with PMWS is the

same age as the pig on the right

Gross: enlargement of the lymph nodes (esp mesentric lymph nodes)

• histo: granulomatous inflammation of the node with large botryoid

(grape-like) intracytoplasmic viral inclusions

Noah’s arkive

Diffuse Granulomatous Lymphadenitis

Postweaning multisystemic wasting syndrome (PMWS):


Neoplastic Diseases of the Lymph Nodes

Primary Neoplasia lymph node neoplasia

* covered in primary

hematopoietic neoplasia

Dr E Aburto

Dr E Aburto

Neoplastic Diseases of the Lymph Nodes

Lymph node metastasis:

• common with carcinomas, melanomas, mast cell tumors, etc

• lymph nodes may be enlarged

• variable effacement of normal architecture

Secondary lymph node neoplasia

Metastasis of mammary

carcinoma to a lymph node

Secondary lymph node neoplasia

pathology of the hematopoietic systempeople.upei.ca/hanna/hemato-l2/hemat-l2-2014web.pdf · •...

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